Differential Level in Co‐Down‐Modulation of CD4 and CXCR4 Primed by HIV‐1 gp120 in Response to Phorbol Ester, PMA, among HIV‐1 Isolates

HIV‐1 enters cells through interacting with cell surface molecules such as CD4 and chemokine receptors. We generated recombinant soluble gp120s derived from T‐cell line‐tropic (T‐tropic) and macrophage‐tropic (M‐tropic) HIV‐1 strains using a baculovirus expression system and investigated the association of CD4‐gp120 complex with the chemokine receptor and/or other surface molecule(s). For monitoring the co‐down‐modulations of the CD4‐gp120 complex, a cytoplasmic domain deletion mutant (tailless CD4), which is not capable of undergoing down‐modulation by itself in response to phorbol ester PMA, was used. Our studies revealed both cell‐type and HIV‐1 strain‐specific differences. We found that T‐tropic gp120s were capable of priming co‐down‐modulation with tailless CD4 by interacting with CXCR4, whereas M‐tropic SF162 gp120 could not after PMA treatment even in the presence of CCR5. Among the T‐tropic HIV‐1 envelopes, IIIB gp120 was the most potent. Furthermore, the ability of gp120 to prime the PMA induced co‐down‐modulation of tailless CD4 appeared to be dependent on the concentration of the principal coreceptor CXCR4. Nevertheless, the observation that IIIB gp120 strongly primed tailless CD4 co‐down‐modulation on human osteosarcoma HOS cells that express undetectable levels of surface CXCR4 raised the possibility that membrane component(s) other than those recently identified can be involved in down‐modulation of the CD4/gp120 complexes.